Squamous cell carcinoma of the skin (SCC) is a common malignancy in the United States and the incidence rate appears to be rapidly increasing. There is experimental evidence from laboratory animal and in vivo studies that selenium intake may reduce skin cancer occurrence, but few epidemiologic studies have examined this. Alpha-tocopherol also inhibits skin cancer formation in certain laboratory animal models, but its role in human skin cancer is presently unclear. Between March 1983 and September 1989, we conducted a randomized clinical trial testing whether beta-carotene reduced risk of nonmelanoma skin cancer. The trial involved 1805 patients from four clinical centers who were less than 85 years of age and had a nonmelanoma skin cancer diagnosis in the recent past. Participants received a dermatologic exam and had blood drawn at study entry, then annually for up to five years. We now propose to use stored plasma specimens, in a nested case-control study to examine whether prediagnostic levels of selenium or alpha-tocopherol are associated with the subsequent occurrence of SCC. Cases will be 130 patients who developed SCC during the follow-up period. Two controls for each case will be randomly selected from patients who did not develop SCC. Selenium determinations will be made using neutron activation analysis. Alpha-tocopherol concentrations will be measured using high-performance liquid chromatography. The results of this study will help elucidate the role of selenium and alpha-tocopherol in the etiology of squamous cell carcinoma of the skin and contribute to our understanding of nutritional factors in cancer development.